Spinocerebellar ataxia (SCA) includes neurodegeneration diseases in which the main locus of pathological change exists in nucleus or neural pathway of cerebellum, brainstem or spinal cord. As a main physical change of SCA, cerebellar ataxia or posterior column ataxia is shown. SCA is classified into hereditary diseases such as hereditary olivo-ponto-cerebellar atrophy, hereditary cortical cerebellar atrophy, Machado-Joseph disease, Friedreich's ataxia, hereditary Dentatorubral pallidoluysian atrophy and the like, and nonheritable diseases such as olivo-ponto-cerebellar atrophy, Shy-Drager syndrome, striato-nigral degeneration, cortical cerebellar atrophy and the like, and critical causes of these diseases have been unknown. Although conditions of diseases and progresses of the condition depend on type of diseases, all of diseases are progressive. The patients are finally confined to their beds and often lead to pulmonitis, asphyxia or sudden death. SCA is neural intractable diseases of unknown causes and investigations of the causes and establishment of an effective method for the treatment have been required.
Because striato-nigral degeneration, olivo-ponto-cerebellar atrophy and Shy-Drager syndrome have many common features in pathological, findings, they can be classified as multiple system atrophy. A definition for classification between spinocerebellar ataxia and multiple system atrophy are indefinite.
Thyrotropin-releasing hormone (TRH) is considered to be effective for treating or amelioration of spinocerebellar ataxia, and the compounds described in Patent Literature 1 and Non-Patent Literature 1 are used for a pharmaceutical composition for treating spinocerebellar ataxia. In Patent Literatures 2 to 7 and Non-Patent Literature 2, it is described that compounds having TRH-like activity are effective for treating spinocerebellar ataxia and TRH derivatives have been developed as a drug for spinocerebellar ataxia. A more excellent pharmaceutical composition for treating and ameliorating spinocerebellar ataxia has been desired.
Patent Literature 8 discloses compounds which show activating effect of central nervous system and which are useful for treating various symptoms caused by hypoactivity of dopamine system, norepinephrine system and acetylcholine system. The chemical structures of the compounds of the present invention are disclosed.
Patent Literature 9 discloses that the compounds of the present invention are useful for treating Parkinson's diseases, and Patent Literature 10 discloses that bioavailability (hereinafter referred to as BA) of the compounds are 4 to 34 times higher than that of TRH or TRH derivatives.
None of the prior art discloses that the compounds of the present invention have particular effect for treating spinocerebellar ataxia or multiple system atrophy.
Patent Literature 1JP 61-33197 APatent Literature 2JP 63-290876 APatent Literature 3JP3-236397 APatent Literature 4JP 6-56886 APatent Literature 5JP 9-157286 APatent Literature 6JP 59-155346 APatent Literature 7JP 60-190795 APatent Literature 8WO98/08867Patent Literature 9WO02/17954Patent Literature 10WO99/53941Non-PatentEuropean Journal of Pharmacology, 1994,Literature 1vol. 271, p. 357Non-Patent“Asu no Shinyaku, Division of drugLiterature 2efficacy, drugs for neurosystem and sensoryorgan-2, drugs for central nervous system,(vol. 2), drugs for peripheral nervoussystem”, Technomics, Inc, published onJul. 22, 2004, page 409